WP760 for Malignant Melanoma Therapy

WP760 用于恶性黑色素瘤治疗

• 批准号: 6828682
• 负责人: ELIZABETH A GRIMM
• 金额: $ 25.46万
• 依托单位: HOUSTON PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-10 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6828682
• 关键词: SDS polyacrylamide gel electrophoresis; antineoplastics; apoptosis; athymic mouse; combinatorial chemistry; cytotoxicity; drug screening /evaluation; melanoma; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; pharmacokinetics; small molecule; terminal nick end labeling; therapy design /development; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Skin cancer is the most prevalent cancer in the USA, and melanoma is the most malignant of skin cancers. The incidence of melanoma in the USA is increasing more rapidly than for any other cancer. Patients with metastatic melanoma have <5% survival after 5 years, and melanoma recently replaced leukemia as responsible for more lost hours in the work place. Currently there are no approved therapies for metastatic melanoma that achieve more than a 20% response rate. The University of Texas, M.D. Anderson Cancer Center currently manages the largest number of melanoma patients in the US. Together with Callisto Pharmaceuticals Inc., which develops small-molecule anticancer drugs, we propose to explore the potential development of a recently discovered novel antimelanoma drug, WP760. WP760, is a bis-intercalating DNA binding drug which has demonstrated remarkable selectivity towards melanoma cells, based on preliminary data from the NCI in vitro anti-tumor screen. Using the Compare Program, an algorithm that compares drug profiles, researchers at the NCI found WP760 to have a highly selective activity against melanoma that was distinctly unique and different from all of the 80,000 other cancer drugs to which it was compared. In this Phase I FLAIR STTR application, we propose to further evaluate WP760's potential as a drug to treat melanoma, with the intent of moving to clinical trials in melanoma and eventual commercialization. We propose optimization of production chemistry and formulation, performance of pharmocokinetics and toxicity in rodents, sensitivity of human melanoma vs. other tumors to growth inhibition by WP760 in vitro, and finally testing of efficacy in a human melanoma xenograft mouse model using systemic administration of WP760 to approach the human use. Successful completion of these objectives will then be followed by a Phase II STTR submission for final preclinical studies, leading to an IND application and clinical trial testing in humans.

描述（由申请人提供）：皮肤癌是美国最普遍的癌症，黑色素瘤是皮肤癌最恶性的。 与任何其他癌症相比，美国黑色素瘤的发病率更快。 5年后，转移性黑色素瘤患者的存活率<5％，而黑色素瘤最近取代了白血病，以导致工作场所损失更多的时间。 当前，尚无批准的转移性黑色素瘤疗法，其疗法的疗法超过20％。 德克萨斯大学，医学博士安德森癌症中心目前管理着美国黑色素瘤患者数量最多。 与开发小分子抗癌药物的Callisto Pharmaceuticals Inc.一起，我们建议探索最近发现的新型抗乳糖药物WP760的潜在发展。 WP760是一种基于来自NCI的体外抗肿瘤筛查的初步数据，对黑色素瘤细胞的选择性显着，对黑色素瘤细胞具有显着的选择性。 使用比较程序（一种比较药物概况的算法），NCI的研究人员发现WP760对黑色素瘤具有高度选择性的活性，该活性与与之比较的所有其他80,000种其他癌症药物不同。 在此阶段I的智能应用程序中，我们建议进一步评估WP760作为治疗黑色素瘤的药物的潜力，目的是转化黑色素瘤和最终商业化的临床试验。 我们提出优化生产化学和制剂，药代动力学的性能和啮齿动物的毒性，人类黑色素瘤的敏感性与其他肿瘤对WP760在体外对生长抑制的敏感性，并最终使用WP760的全身施用人类黑色素瘤异种瘤小鼠模型测试功效接近人类使用。 然后，成功完成这些目标，然后将进行最终临床前研究的II期STTR提交，从而导致IND应用和人类的临床试验测试。